Process for the preparation of alpha, beta-unsaturated carbonyl compounds



rates The invention relates to the preparation of ,B-Ul'lSfituratedcarbonyl compounds from carbonyl compounds, the molecule of which has atleast 2 carbon atoms less.

A number of reactions in which a carbonyl compound is converted into ana,;3-unsaturated carbonyl compound having a greater number of carbonatoms, is described in literature. Of these known reactions thefollowing are mentioned:

1) The aldol-condensation, followed by dehydratation. This reaction canonly be used with a small number of compounds and is applied in industryin a very limited number of cases only; mention may be made here of thepreparation of acrolein from acetaldehyde and formaldehyde.

(2) The Perkin-reaction, in which an aromatic aldehyde is reacted withthe anhydride of an aliphatic acid in the presence of a salt of the sameacid to form an 11,5- unsaturated acid.

v (3) The Claisen-reaction, in Which an aromatic aid..- hyde is reactedwith ethylacetate or a similar ester in the presence of metallic sodiumand a trace of alcohol. In this reaction the ester of an u,8-unsaturated acid is E e formed.

'(4) The Reformatsky-reaction, in which a carbonyl compound is reactedwith an a-halo-ester and zinc; after hydrolysis and dehydratation theester of an nip-unsaturated acid is obtained.

(5) The coupling of a carbonyl compound with a metal derivative ofethoxy-ethyne, in which after-hydrolysis an ethoxy ethyne carbinol isformed, which, by treatment with an acid, can be converted into an:,[3-1111Sflll11'2tl6d ester or-after partial reduction of the ethynebondinto an a,,3-unsaturated aldehyde.

It was found now that cap-unsaturated carbonyl compounds can be preparedfrom carbonyl compounds having at least 2 carbon atoms less, by reactingthem with an alkyne compound in an indilferent solvent in the presenceof a Lewis acid.

The reaction taking place in the present process can be represented bythe following equation:

r I 1 R: Lewis acid l /C==O 3505034 /C=C-([3Rl R2 R: (l

in which R represents hydrogen, an aliphatic, aromatic, araliphatic oralicyclic hydrocarbon rest,

R represents hydrogen, a substituted hydroxyl'group, an

atent ice ' group, an aliphatic, aromatic, araliphatic or alicyclichydrocarbon rest. 1

An advantage of the present process over the known processes is that itcan be applied with different compounds, by means of which a very greatnumber of compounds, part of which was difiicult of access so far, canbe prepared in this manner.

Other advantages are that the process can be carried out very easily,that high yields are obtained, that it quickly leads to the objectrequired and that it takes place under mild conditions.

Lewis acids that are very suitable to be used in the present processare, for example, metal halides, such as aluminium chloride, ferricchloride, stannic chloride, boron fluoride and zinc chloride.

In particular the compounds that by coordination with the oxygen atom ofthe carbonyl group activate the carbon atom of that group-render itpositive-have proved good catalysts. Besides the said metal halogenidessuch as for example compounds as boric acid esters and aluminiumsulphate are also quite suitable. Preferably BF is used, because with itslightly reactive carbonyl groups,

too, can be activated and because with this compound added catalyst ispossible, which is more difiicult when the gaseous BB, is used.

The reaction is preferably carried out at a temperature below 0" 0.,because at higher temperatures polymerisation of the alkyne compound mayoccur under the influence of the Lewis acid, which may give rise.todiscolouration and contamination of the reaction product.

As reaction medium solvents can be used that do not take part in thereaction. without reactive groups, such as hydroxyl, keto, and aminogroups. Solvents that qualify for the purposeare, for example, carbondisulfide, ethers, dioxane, petroleum ether, chloroform, and aromatichydrocarbons. ably diethyl-ether is used, because most compounds readilydissolve in it, because good yields are obtained when it is used andbecause the ether can be easily removed by evaporation when the reactionis completed. High yields are also obtained with carbon disulfide assolvent.

The amounts of the reaction components are preferably chosen so thatthere are equivalent amounts of the carbonyl compound and the alkynecompound. In the case of an excess of the carbonyl compound there is apossibility that when the reaction is completed, this excess polymerisesunder the influence of the Lewisacid, thus giving rise to contaminationof the reaction mixture.

An excess of the alkynecompound i-s-likewise less des'ira-ble, becauseafter completion of the reaction desired,

this excess may react with the ix-unsaturated:carbonyl compound formed,which causes the reaction mixture to become contaminated and the yieldto decrease.

The following examples illustrate the invention. Yields are alwayscalculated on the basis of the carbonyl compound.

In general they are solvents,

Prefer-,.

3. EXAMPLES Cinnamic Acid Ethyl Ester 21 g. of benzaldehyde aredissolved in 100 ml. of ether, whereupon after cooling-to C., 28 g. ofborontrifluoride etherate are added to this solution, after which 14 g.of ethoxy-ethyne are slowly added dropwise; the temperature of themixture being kept at 0 C. After standing 24 hours the reaction mixtureissuccessively washed with a solution of potassium carbonate and water.After drying over sodium sulphate the ether is evaporated, whereupon thecinnamic acid ethyl ester is obtained by distillation in vacuum. Boilingpoint (15 mm. Hg): 140 C., yield 90%.

Cinnamic'Acid Ethyl Ester In the same way as described in Example I thecinnamic acid ethyl ester is prepared, this time, however, by using 37g. of magnesium bromide instead of boron trifluoride. Yield 72%.

III

Crotorzic Acid Methyl Ester pfl-Dimethyl Acrylic Acid Ethyl Ester In themanner as described in Example I the 13,l3-dimethyl acrylic acidethylester is prepared starting from 518 g. of acetone, 7 g. of ethoxy ethyneand 14.2 g. of BF etherate. Yield 72%. Boiling point at a pressure of30mm. Hg is 61' C. v

a,fl-Dimethyl Thiocrotonic Acid Ethyl Ester A solution of 11.6 g. ofacetone and 25 g. of BF etheratc is prepared in 50 ml; of ether. Thissolution is cooledto l0 C. To the cooled solution 20 g. of ethylthiopropyne are added, after'which the solution is allowed to stand for20hours at -10 C. The reaction mixture is' washed with a solution ofsodium carbonate and distilled water, and "dried with sodium sulphate.The ether is evaporated and the a,;8-dirnethyl thiocrotonic acid ethylester-formed, purified by distillation under vacuum. This ester, whichhas not been described before in literature, hasa boiling point'of 90 C.at a pressure of mm. Hg.

acted.; 'Ihefi-ethoxy-crotonic acid ethyl ester is obtained in. purecondition by vacuum distillation; the boiling point VII fl-Eth0xyAcrylic Acid Ethyl Ester The fl-ethoxy acrylic acid ethyl ester isobtained by reacting in the manner of Example I 14.8 g. of ethylformate,14 g. of ethoxy-ethyne in 50 ml. of ether under the influence of 20 g.of BF -etherate. Yield 65%. The compound is purified by vacuumdistillation and boils at a pressure of 15 mm. Hg at C.

VIII

S-Metlzyl-Thiocrotonic Acid Ethyl Ester- The fi methyl-thiocrotonic acidethyl ester is obtained by reacting in the manner of Example I, 11.6 g.of acetone, 17.6 g. of ethylthio-ethyne in 50 m1. of ether under theinfluence of 25 g. of BF -etherate. The product distils at'a temperatureof 65 C. at a pressure of 15 mm. Hg.

Acrylic Acid Ethyl Ester The acrylic acid ethyl ester is prepared in themanner of Example I, by reacting 6.0 g. of formaldehyde and 14 g. ofethoxy-ethyne in 30 m1. of ether in the presence of 25 g. of BF-etherate. The compound distils at about C. Part of the product isobtained as polyacry1ate.-

fl-DimethylaminoeAcrylic Acid Ethyl Ester .andJrimesic Acid-Tri-EthylEster By putting 14 g. of ethoxy-ethyne in 20 g. of dimethylformamidecontaining 30 g. of BF -etherate and allowing the mixture to stand for24 hours at 0 C. the fl-dimethylamino acrylic acid ethyl ester isformed. It is obtained by washing with a potassium carbonate solution at10 C. and extraction with, ether, after which theetherisp-Methyl-u-Ethyl-crotonic Acid Ethyl Ester The B-methyl-a-ethylcrotonic acid ethyl ester is prepared in the manner of Example I, byreacting 11.6 g. of

acetone, 19.6 g. of ethoxy butyne and 28.4 g .,ofBF etherate in'60 ml.of ether. Yield 78%. Boiling point 166-168 C.

XII

Benzal Acetophenone 21.2 g. of benzaldehyde are dissolved in 50 ml. ofether, to which solution 20 g. of BF -etherate are added at roomtemperature. Then 20.4 g. of phenyl acetylene are added, after which themixture is left to stand one night;

Benzal-Acetophenone In the manner of Example XII benzal-acetophenone-isprepared. Instead of boron trifluoride aluminium chloride is used as acatalyst. Now the yield is 48%.

5 XIV Benzal-Acetophenone In the manner of Example XIIbenzal-acetophenone is prepared, but instead of boron trifluoridemagnesium bromide is used as a catalyst.

The magnesium bromide used as a catalyst is prepared by the reaction ofbromine on a suspension of magnesium in ether. Yield of purebenzal-acetophenone:

fi-lonylidene Acetic Acid Ethyl Ester XVI Ethyl Ester of the VitaminA-Acid 25.8 g. of the so-called C -ketone of the vitamin A-synthesis aredissolved in 70 ml. of ether, whereupon after cooling to C., 14.2 g. ofBF -etherate and 7 g. of ethoxy-ethyne are added to the solution. Afterstanding 20 hours the ethyl-ester of the vitamin A-acid is obtained inthe manner of Example XV. Yield 65% XVII 3-Ethylene Glycol Ketal of A-3,11-Diket0- Rregnadicne-ZJ-carb0xylic Acid Methyl Ester 25.2 g. of the3-ethylene glycol ketal of Ar -3,11,17- triketo-androstene are dissolvedin 150 ml. of ether. After cooling to C.,. 5.6 g. of methoXy-ethyne and14.2 g. of BF -etherate are added to the solution, after which themixture is allowed to stand for 24 hours at ---5 C. The reaction mixtureis Washed with a solution of sodium carbonate and water, and then driedover sodium sulphate. After evaporation of the ether the residue isrecrystallised a few times from a mixture of ethyl acetate and petroleumether to obtain the pure product; melting point 188 0.; Yield 58%.

XVIII According to thefollowing example the reaction products of TablesI and II are prepared.

0.1 molecule of boron trifluoride etherate diluted with 50 ml. ofabsolute ether are passed into a flask fitted with stirrer, droppingfunnel and thermometer. After cooling to 0.1 molecule of the carbonylcompound (aldehyde, ketone, ester, acid amide) dissolved in 50 ml. ofabsolute ether is added in -30 minutes, when usually a slight heateffect is noticeable and in some cases a precipitate of a BF -complex isformed. Next 0.1 molecule of ethyne ether dissolved in 75 ml. ofabsolute ether is added dropwise in 2-3 hours at l0'i.' During theaddition evolution of heat takes place and in most cases a light yellowto brown precipitate is formed.

After bringing the temperature of the reaction mixture up to 0hydrolysis takes place with a solution of %v potassium carbonate (0.1molecule K CO which is added in 20-30 minutes. Under considerableevolution of heat decomposition of the complex takes place. After theevolution of carbonic acid has ceased the ethereal solution isseparated, washed with a K CO solution and water, and dried on CaSOether the reaction product is obtained by fractionated distillation.

The carbonyl compounds mentioned in Table I have been reacted withethoxy-e-thyne as ethyne ether.

TABLE I Boiling point or Yield Carbonyl compound Reaction productmelting point in percen 1:

formaldehyde (trioxacrylic acid ethyl- B.P. 98-104 37 one). ester.acetaldehyde crotonic acid B.P. 128-132 I v 41 ethylester.propionaldehyde fi-ethylacrylic B.P. 50-64710 28 acid ethylester. mm. 1butyraldchyde B-propylacrylic B.P. 7298/11 22 acid ethylester. mm.acrolein fi-vinylacrylic B.P. 50-60/10 29 acid ethylester. mm.crotonaldehyde sorbic acid I B.P. 75.576/10 52 ethylester. mm.benzaldehyde cinnamic acid B.P. 9498.5/0.8 48-50 ethylester. mm.aniscldehyda p-methoxy cinna- M.P. 47.549.. 54

mic acid ethylester. p-nitrob enzaldehyde p-nitrocinnamic M.P. 134.5136.25

acid ethylester. a-naphthaldehyde B-naphthyl-(D- M.P. 37-37.5... 50

acrylic acid ethylester. thiophehaldehyde. fl-(a-thienyb-acryl- B.P.8086/0.51 53 ie acid cthylester. mm. acetone; B-methylcrotonic B.P.140156 82 7 acid ethylester. butanone B-methyl-a, B.P. 170172/ 71pentenic acid 770 mm. ethylester. diethylketonc fl,,B-diethylacrylicB.P. 6969.5/ 59 acid ethylester. 10 mm. acctophenone 3-methy1cinnamicB.P. 91115/ 50 acid ethylester. 0.7 mm. cyclopentanone.-.cyclopentylidcne B.P. 8888.5/ 65 acetic acid ethyl- 10 mm. es er.cyclohexanone cyclohexylidene B.P. 102105/ 77 acetic acid ethyl- 12 mm.

ester. cycloheptsnone cycloheptylidene B.P. 115116/ 65 acetic acidethyl- 10 mm.

es er. fl-ionone fi-ionylidene acetic B.P. 126131/ 50 acid ethylester.0.5 mm. ethylformiatc B-ethoxy acrylic B.P. 8690/ acid ethylester. 13mm. dimethylformamidc-- fi,fl-di1nethylacryi- B.P. 6363.5/ 25 to acidethylester. 1 mm.

In an analogous manner acetone has been reacted with the alkyn compoundsmentioned in Table II.

For the reaction products obtained and further details see said table.

TABLE II Yield Alkyn compound Reaction product Boiling point in percentisobutoxypropyne a,fl-dimethy1 crotonic 70-86/15 mm...-

acid isobutyl ester. 7 math oxyheptynea-pcntyi-fl-methyl 44.044.2/ 0.4"42 crotonic acid mm.

' methyl-ester. ethoxyisopentync... a-isopropyl-fl-methyl- 6970/10 mm.41

crotonic acid ethylester. cthoxyheptyne a-pentyl-B-methyl 46.046.2/0.251

crgtonic acid ethylmm. es er. methoxypentyne. a-propyl-B-methyl65.566.5/10 59 crotonic acid mm. methyl-ester.

After evaporation of the What we claim is: 1. Process for thepreparation of a,fi-unsaturated carbonyl compounds of the generalformula:

in which group, a substituted amino group, an aliphatic, aromatic,araliphatic-andalicyclic hydrocarbon radical R representstaamember ofthe group consisting of hydrogen, an alkyl, aryl, aralkyl and analicyclic hydrocarbon, radical and R representsa member of the groupconsisting of an alkoxy group, an alkylthio group, an aliphatic,aromatic; ariliphatic and alicyclichydrocarbon radical,

comprising reacting-a carbonyl compound of the general formula R==C=Owith ,an alkyfle compound of the gem.

5; Process according to claim 1, in which the reaction is carried out incarbon disulfide,

6. Process according to claim 1, in which the reaction is carried out inthe presence of a Lewis acid which, by coordination with the oxygen atomof the carbonyl group in the carbonyl compound, activates the carbonatom of that group.

No references cited.

1. PROCESS FOR THE PREPARATION OF A,B-UNSATURATED CARBONYL COMPOUNDS OFTHE GENERAL FORMULA: